The present invention relates to the treatment of ailments in humans and other mammals, and more particularly, to an apparatus and method for continuous flow delivering pharmaceutical compounds and genes into live cells of a patient.
It has long been known that it would be desirable to target certain cells within the body with specific pharmaceutical compounds. For example, in the treatment of certain types of cancer with chemotherapy it is necessary to use a high enough dose of a drug to kill the cancer cells without killing an unacceptably high number of normal cells. If the chemotherapy drug could be inserted directly inside the cancer cells, this objective could be achieved. However, some of the best anti-cancer drugs, for example, bleomycin, normally cannot penetrate the membranes of certain cancer cells.
Similarly, certain diseases could be treated by introducing desired genes into the specific cells of the patient. At present, most gene therapy experiments have utilized retroviruses as the carrier of the gene into the cells. When a retrovirus enters a target cell, it integrates essentially randomly in the genome and thus has the potential for introducing mutational damage by the mere fact of its insertion. If the virus integrates adjacent to an oncogeny, malignant transformation of the target cell can result. Many of these drawbacks can be alleviated by using electroporation for gene transfer.
It is known that genes and other molecules and macromolecules such as pharmaceutical compounds can be incorporated into live cells through a process known as electroporation. The genes or other molecules and macromolecules are mixed with the live cells in a buffer medium and short pulses of high electric fields are applied. The high electric field pulses cause the cell membranes to become transiently porous and the genes or macromolecules enter the cells. There they can modify the genome of the cell. There is good evidence that electroporated genes can recombine with their homologous host gene. Examples of the prior art are: U.S. Pat. No. 4,970,154 of Chang, U.S. Pat. No. 5,098,843 of Calvin and U.S. Pat. No. 5,128,257 of Baer.
The incorporation of drugs into red blood cells via electroporation as well as the incorporation of genes into white blood cells via electroporation have both been demonstrated. The selective incorporation of genes into white blood cells in whole blood via electroporation has also been demonstrated. The electroporation of cells in a flow through system utilizing a venturi in a static field has been proposed by Calvin in U.S. Pat. No. 5,098,843.
Heretofore, an apparatus and method have not been provided to permit electroporation mediated, ex vivo, intra cellular drug and gene delivery through the blood vessels of a living patient. It would be desirable to provide such an apparatus and method because it would permit gene therapy of living patients by genetically modifying their lymphocytes. Such an apparatus and method would also be beneficial in providing a means for delivering drugs to selected tissues and organs of a living human body by encapsulating them into red blood cells. In general, such an apparatus and method would be advantageous in providing a means of delivery of antibodies, proteins, or other macromolecules into the red or white blood cells of a living patient.